Bone production by osteoblasts and bone resorption by osteoclasts is critical for normal bone development and remodeling. Excessive resorption is a key pathogenic component in osteopenic conditions such as osteoporosis, arthritis, periodontitis and certain malignancies. Bone resorption is regulated by a complex system of hormones and locally-produced cytokines that stimulate osteoblasts and stromal cells to express Receptor Activator of NF-κB Ligand (RANKL), which results in the differentiation and activation of osteoclasts. The processes by which osteoclast differentiation and activation occur are currently not well understood.
Additional intracellular signaling pathways may also be important regulators of osteoclastic resorption and bone production by osteoblasts. The identification of the molecules that mediate differentiation and activation of osteoclasts and production of bone by osteoblasts may lead to new methods for regulating bone resorption and bone mineral density, and to new treatments for osteopenic conditions.